Associations among stress perception, clinical symptoms, and hippocampal subfield volumes in first-episode patients with schizophrenia.

Background: Hippocampal neurogenesis shapes adaptation and improves responses to stress. Patients with schizophrenia show marked functional impairment and abnormal stress sensitivity. However, it remains unclear how structural abnormalities in specific hippocampal subregions are related to altered perceived stress and clinical symptoms in schizophrenia. Methods: We recruited 97 first-episode patients with schizophrenia (FEPS) and 47 healthy controls (HC). Perceived stress and psychopathology were assessed using the Perceived Stress Scale (PSS) and the Positive and Negative Syndrome Scale (PANSS), respectively. Structural MRI was acquired on a 3.0-T scanner, and hippocampal subregions were segmented using validated, standardized protocols. Left and right subregional volumes were summed to obtain calculate bilateral volumes. Results: Compared to HC, the FEPS group showed higher perceived stress, reduced fimbria volumes, and increased hippocampal tail volumes after adjustment for intracranial volume, age, sex, and education. In HC, several hippocampal subregion volumes were positively correlated with stress perception; however, these associations were absent or disrupted in FEPS. In FEPS, stress perception was positively associated with positive and anxiety/depression symptoms. Additionally, specific hippocampal subfield volume was positively associated with negative symptoms. Conclusions: FEPS was characterized by aberrant perceived stress, altered hippocampal subregional volumes, and disrupted links between stress perception and hippocampal structure. The interrelations among stress, clinical symptoms, and hippocampal subfields suggest altered psychological and neurobiological processes underlying stress regulation processes in FEPS.